The present invention relates to lactam compounds and a therapeutic agent for diabetes which contains the compound(s) as the active ingredient.
The medicinal treatment for type II diabetes is employed when a sufficient improvement of a patient cannot be attained by dietetic treatment or kinetotherapy, and there have been developed pharmaceutical preparations containing insulin that is an endogenous hormone for controlling the hypoglycemic function and also peroral hypoglycemic agents having an effect of accelerating insulin secretion or improving peripheral insulin resistance. At present, the main medicinal treatment for type II diabetes comprises using a peroral hypoglycemic agent for strictly controlling the blood sugar level. However, when insulin-like effect sufficient for controlling the blood sugar cannot be obtained, the insulin therapy is mainly employed. On the other hand, the insulin therapy is the only treatment for patients with type I diabetes because they have lost the insulin secretion capacity.
Although the insulin therapy is thus an important treatment method, use of injection causes problems that the treatment technique is complicated and that the patient must be trained. Under these conditions, an improvement in the administration method is eagerly demanded from the viewpoint of the compliance. Recently, it was tried to develop methods for administering insulin in the form of non-injection preparations instead of the insulin injection. However, those methods have not been practically employed because of a low absorption efficiency or unstable absorption.
It is one of the important hypoglycemic functions of insulin that it increases the sugar-transporting capacity of peripheral cells to incorporate the sugar in the blood into the cells and, as a result, the blood sugar level is lowered. If a new oral medicine capable of lowering the blood sugar level by increasing the sugar-transporting capacity of peripheral cells is found, it would became the therapy in favor of the patients. However, such a medicine has not yet been developed.
On the other hand, as for the lactam compound, Khim.-Farm. Zh., 25 (11), (1991) and Pharmaceutical Chemical Journal. 25 (11), 768 (1991) disclose compounds of general formula (I) given below, wherein B represents a benzene ring, —X— and —Y— each represent —NH—, —Z— represents —CH2—, —W— represents —NH— and —A(R2)(R3)(R4) represents a phenyl group, 4-bromophenyl group, 4-hydroxyphenyl group, 4-methoxyphenyl group, 2-hydroxyphenyl group, 3,4-dimethoxyphenyl group or 3-methoxy-4-hydroxyphenyl group. It is described therein that those compounds have no anxiolytic effect, antispasmodic effect or cardiotonic effect.
Journal of the Pharmaceutical Society of Japan, 715–20 (1986) and Chem. Pharm. Bull., 3724–9 (1984) disclose compounds of general formula (I) given below, wherein B represents a benzene ring, —X— represents —NH—, —Z— represents —CR6R7—, —W— represents —NH— and R6 and R7 each represent a methyl group. It is described therein that those compounds have a weak analgesic effect.
Synthesis, 937–8 (1987) discloses a compound of general formula (I) given below, wherein B represents a benzene ring, —X— represents —NH—, —Z— represents —CO—, —W— represents —NR1— and R1 represents p-tolyl group. However, the activity of this compound is not described therein.
Journal of the Pharmaceutical Society of Japan, 1004–8 (1984) discloses compounds of general formula (I) given below, wherein B represents a benzene ring, —X— represents —NH—, —Y— represents —S—, —Z— represents —CR6R7—, W represents —NH— and R6 and R7 each represent a methyl group. It is described therein that those compounds have a weak sterilizing effect.
Journal of Organic Chemistry, 4367–70 (1983) also discloses compounds of general formula (I) given below, wherein B represents a benzene ring, —X— represents —NH—, —Y— represents —S—, —Z— represents —CH2— and —W— represents —O—. However, the activity of this compound is not described therein.